Project Summary/Abstract Chemosensory responses are critical components in the control of several essential behaviors of insects that are vectors for pathogens responsible for many important human diseases. In particular, olfaction plays a major role in host seeking and oviposition preference/selection behaviors of blood-feeding female mosquitoes and, as such, constitutes a critical component of the mosquito's ability to transmit diseases such as malaria, dengue, yellow fever, Zika and West Nile virus encephalitis. Within this context, and together with our colleagues, we have undertaken a molecular, cellular and organismal examination of several elements of the olfactory signal transduction cascade in the principal African malaria vector mosquitoes Anopheles gambiae, An. coluzzii, An. arabiensis and An. funestus. An increased understanding of olfactory mechanisms and their underlying chemical cues provides insight into the processes of insect behavioral responses in general and disease transmission in particular and would likely be instrumental in the development of novel mosquito control strategies. In this context we have made significant progress in the characterization of several aspects of olfactory process in mosquito systems leading to, among other things, the identification and functional characterization of a family of odorant receptor proteins that lie at the heart of the olfactory signaling pathway. Building on those advances, this proposal for competitive renewal focuses on extending several elements of our ongoing program including characterization of: (1) the in vivo impact of biologically relevant Plasmodium falciparum infections on OR expression and OR-based olfactory receptivity, (2) the olfactory physiology and functional role of labellum ORs in An. coluzzii and (3) an examination of anthropophily via a comparative analysis of OR expression and functionality across Anophelines.